pH driven invasion into tumor - Research into cancer diagnostics (Nov/27/2007 )
Compounds which become lipophilic at low pH can selectively anchor onto cells within a tumor, which are characteristically acidic.
Here is a news segment from Oregon Public Broadcasting radio describing the experiments and announcing an upcoming paper. To hear the news segment, click on the link below and press the "listen" button on the new window.
http://news.opb.org/article/osu-team-uses-...hemicals-tumor/
Thank you Jon Moulton.
I am waiting for their paper.
I am waiting for their paper.
http://www.ncbi.nlm.nih.gov/sites/entrez?D...Search=17900997
Mata JE, Dyal LA, Slauson ME, Summerton JE, Loehr C, Tyson AR, Rodriguez-Proteau R, Gustafson SB. Tumor imaging using technetium-99m bound to pH-sensitive peptides. Nanomedicine. 2007 Sep 25; [Epub ahead of print]
Solid tumors often display metabolic abnormalities that consistently produce low pH in the extracellular space of poorly perfused tissue. These acidic regions may provide a mechanism for drug targeting. Peptides have been designed in such a manner that they exist in an anionic hydrophilic form at the pH of normal tissues, but then undergo a sharp transition to a non-ionic lipophilic form at reduced pH. Peptides were labeled with fluorescein or technicium-99m (99mTc) and evaluated in vitro and in two murine models of cancer. Our studies suggest that PAP-1, an 18 amino acid pH activated peptide with a pH of transition between hydrophilic and lipophilic forms (pT) of 6.4, will deliver fluorescein and 99mTc to tumors. Activation of PAP-1 by low pH and penetration into the plasma membrane of cells and tumors were confirmed using flow cytometry, fluorescence microscopy, and gamma scintigraphy. These results support our central hypothesis that PAP-1 may enable the selective delivery of macromolecules to tumors. This technology has potential for exploiting a common property of tumors to achieve highly specific medical intervention.
Thank you Jon Moulton for letting me know that this paper is in press.
I have the full text of this paper. 
Dr. Jon Moulton, Thank you.
Minnie Mouse, Could I have a copy of it? Thanks.
Minnie Mouse, Could I have a copy of it? Thanks.
check your pm.
News is spreading a bit.
http://www.gtconnect.com/articles/2007/11/..._cancercure.txt
It's fun to see the media picking up on a project.
Very impressive.
Dr. Moulton, what is possibility that this peptide becomes LDL-associated while in the blood and tumor-targeted secondary to the pH induced precipitation/membrane partition for this GALA-like peptide?
We've not tested LDL-binding. Our focus at Gene Tools has shifted from the peptides to small molecules that enter tumor cells by a similar pH-dependent mechanism. John Mata's group will likely pursue the peptides, so if anyone is going to test LDL affinity it will likely be their project.
Very interesting idea.
In future, the cancer patients may suffer less side effect from the chemotherapy.